The goal of this project is to define the role of androgens and estrogens in the sexual differentiation process. We will utilize androgen-insensitive mutants, testicular feminized (Tfm) rats and mice, which differ in their responsiveness to androgens, having a selective loss in their androgen receptor system but not in their estrogen receptor system. We will compare differences and similarities both between genotypes within species and between species to elucidate the relationship between specific hormone-receptor systems and the processes of sexual differentiation. Initial studies will define the behavioral potential of the Tfm mice, such work has already been completed with tfm rats. We will then manipulate the early hormonal stimulation by prenatal treatment. Biochemical studies in neonatal rats will determine whether our manipulations are having their putative effects. Finally, we will utilize females that carry the Tfm gene to dissect the relationship between hormone binding and responsiveness to androgens. These studies will provide unique information on the role of estrogens and androgens in masculinization. Wild-type rats will be utilized to determine the effects of perinatal treatment with the potent non-aromatizable synthetic androgen on the development of female sexual behavior. Parallel biochemical studies will determine the intracellular effects of this treatment. The results will provide information as to the role of estrogen in defeminization.